Comparison of the Behavior of Perivascular Cells (Pericytes and CD34+ Stromal Cell/Telocytes) in Sprouting and Intussusceptive Angiogenesis

Abstract

Perivascular cells in the pericytic microvasculature, pericytes and CD34+ stromal cells/telocytes (CD34+SCs/TCs), have an important role in angiogenesis. We compare the behavior of these cells depending on whether the growth of endothelial cells (ECs) from the pre-existing microvasculature is toward the interstitium with vascular bud and neovessel formation (sprouting angiogenesis) or toward the vascular lumen with intravascular pillar development and vessel division (intussusceptive angiogenesis). Detachment from the vascular wall, mobilization, proliferation, recruitment, and differentiation of pericytes and CD34+SCs/TCs, as well as associated changes in vessel permeability and functionality, and modifications of the extracellular matrix are more intense, longer lasting over time, and with a greater energy cost in sprouting angiogenesis than in intussusceptive angiogenesis, in which some of the aforementioned events do not occur or are compensated for by others (e.g., sparse EC and pericyte proliferation by cell elongation and thinning). The governing mechanisms involve cell–cell contacts (e.g., peg-and-socket junctions between pericytes and ECs), multiple autocrine and paracrine signaling molecules and pathways (e.g., vascular endothelial growth factor, platelet-derived growth factor, angiopoietins, transforming growth factor B, ephrins, semaphorins, and metalloproteinases), and other factors (e.g., hypoxia, vascular patency, and blood flow). Pericytes participate in vessel development, stabilization, maturation and regression in sprouting angiogenesis, and in interstitial tissue structure formation of the pillar core in intussusceptive angiogenesis. In sprouting angiogenesis, proliferating perivascular CD34+SCs/TCs are an important source of stromal cells during repair through granulation tissue formation and of cancer-associated fibroblasts (CAFs) in tumors. Conversely, CD34+SCs/TCs have less participation as precursor cells in intussusceptive angiogenesis. The dysfunction of these mechanisms is involved in several diseases, including neoplasms, with therapeutic implications.

Delimiting CD34+ Stromal Cells/Telocytes Are Resident Mesenchymal Cells That Participate in Neovessel Formation in Skin Kaposi Sarcoma

“…The characteristics and distribution of the CD34+SCs/TCs around apparently unaffected skin vessels and appendages in early KS lesions agree with those previously described in several conditions [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ], creating microenvironments within the tissues (a contribution to maintenance and modulation of local homeostasis) [ 21 , 31 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ]. Likewise, the ability of CD34+SCs/TCs to envelop perivascular inflammatory infiltrates in KS is also consistent with their role in retaining and modulating the immune cells [ 31 , 53 , 54 , 55 , 56 , 57 ], allowing us to explain the presence of an inflammatory component around some intussusceptive pre-existing blood vessels within neovessels (vessels into vessels: a promontory sign in KS).…”

Roles of telocytes dominated cell–cell communication in fibroproliferative acute respiratory distress syndrome

“…67 Recent reports showed that tubal TCs are indirectly involved in local angiogenesis, particularly the CD34 + TCs subtype. 68 These TCs dissociated from their perivascular niche, formed a composite structure with fibrin and fibronectin, proliferated and differentiated to be stromal cells during granulation tissue formation. 69 Additionally, TCs also express measurable quantities of pro-angiogenic microR-NAs (let-7e, 10a, 21, 27b, 100, 126-3p, 130a, 143, 155 and 503).…”

“…Several studies found that TCs could inhibit microvascular endothelial cell apoptosis and promote angiogenesis in myocardial infarction and in chronic inflammation of the uterus and ovaries, such as uterine myoma 67 . Recent reports showed that tubal TCs are indirectly involved in local angiogenesis, particularly the CD34 + TCs subtype 68 . These TCs dissociated from their perivascular niche, formed a composite structure with fibrin and fibronectin, proliferated and differentiated to be stromal cells during granulation tissue formation 69 .…”

The role of pericyte in ocular vascular diseases

“…Additionally, pericytes can differentiate into non-mesenchymal cells, such as neurons. Notably, pericytes derived from skeletal muscle have been reported to differentiate into the high class Ⅲ beta-tubulin (Tuj-1) expressing neurons [39] .…”